SmithKline Beecham Pharmaceuticals’ cysteinyl leukotriene receptor antagonists: Pranlukast (SB 205312; Ono-1078; Onon), Pobilukast (SK&F 104353) and SK&F 106203

SmithKline Beecham’s (SB) entrance into the cysteinyl leukotriene (Cys-LT) research arena began around 1976 with the creation of an “SRS-A” antagonist feasibility study at Smith Kline & French Laboratories. Following the information in the literature in 1979 and 1980 that the Cys-LTs were responsible for the physicochemical and biological properties of the “slow reacting substance of anaphylaxis” (SRS-A), increased attention and resources were focused on Cys-LT research, which was directed towards identifying novel therapeutics which will inhibit the synthesis of the Cys-LTs (5-lipoxygenase (5-LO) inhibitors) or block the effects of the Cys-LTs (receptor antagonists). In this chapter only the latter strategy will be reviewed. In addition to the internal SB discovery activities to identify Cys-LT receptor antagonists for potential clinical development, a compound, pranlukast (Ono-1078; SB 205312; Onon), was in-licensed from Ono Pharmaceuticals. The pharmacological properties of pranlukast, and the key compounds from SB’s own medicinal chemistry efforts, namely pobilukast (SK&F 104353) and SK&F 106203, will be presented.